The 1918 global influenza pandemic killed as many as 100 million people, …

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As regularreaders of Nobel Intent will know, the avian influenza virus H5N1 has been responsible for a lot of sleepless nights among the public health community (and latterly, the biosecurity community). Back in 2005, when we knew much less about the virus, the thought of an airborne pathogen with 70 percent mortality was truly terrifying. Since then, mortality estimates have dropped a little, but not much. But are those estimates completely off the mark? A paper published in Science makes the case that they are.

Influenza pandemics have the potential to rack up giant bodycounts. The outbreak of H1N1 in 1918-1919 killed anywhere between 50 and 100 million people, yet it only had a mortality rate of two percent. Knowing that, it’s not hard to see why a form of H5N1 that spread from person to person inspires terror. Thankfully, the required combination of mutations haven’t happened outside of a couple of research labs, and civilization as we know it is still standing.

But the fears of an H5N1 pandemic are largely based on its high mortality rate. Is the accepted H5N1 mortality rate of 60 percent plausible? That’s the question that a trio of researchers at New York’s Mount Sinai School of Medicine have looked at.

First off, where did the figure of 60 percent (technically 58.6 percent) come from? Well, since 2003, the World Health Organization have been tracking H5N1 infections, and has documented 573 cases, 58.6 percent of which were fatal. But as the authors point out, most H5N1 infections occur in resource-poor areas, with correspondingly poor access to healthcare. It's possible that there are cases that aren't fatal, but aren't recorded by the WHO. Can we be sure that the 573 cases recorded by WHO represent the true disease burden?

The authors conducted a meta-analysis of 20 previous studies, encompassing nearly 13,000 people, and used the presence of H5N1 antibodies as a marker for H5N1 infection. If H5N1 really did kill more than half of those infected, there should be very few subjects positive for H5N1 antibodies. This wasn’t the case; between one and two percent of the studies’ participants showed evidence of prior H5N1 infection.

It's worth mentioning that the senior author of this paper, Peter Palese, has published a similar argument in the past. At the recent panel discussion of H5N1 risks, however, his work was attacked as being far outside the scientific mainstream. Detecting past virus exposure is technically very challenging, and Palese's fellow panelists argued that he's set the bar way too low when it comes to evidence of asymptomatic infection.

If Palese is right, however, perhaps it shouldn't surprise us. Influenza viruses that we know can be transmitted from person to person often merely cause mild infections that resolve without treatment. The WHO’s stringent criteria for confirmed H5N1 cases may also make it unlikely that mild cases would be flagged and included in the statistics. (But it is also true that there may be fatal cases that have not been recorded.)